Carlo M. Croce

My laboratory has been involved in the studies of the genetics of human leukemias and lymphomas and of solid tumors. Also, my group has continued studies of the molecular genetics of chromosomal translocations involving llq23. They have cloned and characterized several genes that fuse with the ALL-1 gene in acute leukemias, identified a transactivating domain and a repressor domain in the ALL-1 protein, knocked out the ALL-1 gene in embryonal stem (ES) cells by homologous recombination, and determined that double knock out of the ALL-1 gene results in a block in hematopoietic differentiation. We have also described a novel genetic mechanism of leukemogenesis where the ALL-1 gene fuses with itself and named this mechanism "ALL-1 self-fusion." Such a mechanism is involved in five to ten percent of human acute myelogenous leukemias. We have also cloned a gene at 14q32.1 that is involved in the pathogenesis of most chronic T cell leukemias and low-grade T cell lymphoma. This gene, named TCL-1, represents the prototype of a new family of oncogenes involved in either lymphoid cell proliferation and/or survival.